The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken

Comparative genomics of nucleosome positions provides a powerful means for understanding how the organization of chromatin and the transcription machinery co-evolve. Here we produce a high resolution reference map of H2A.Z and bulk nucleosome locations across the genome of the fly D. melanogaster, and compare it to that from the yeast S. cerevisiae. Like Saccharomyces, Drosophila nucleosomes are organized around active transcription start sites in a canonical −1, NFR (nucleosome-free region), +1 arrangement. However, Drosophila does not incorporate H2A.Z into the −1 nucleosome and does not bury its transcriptional start site in the +1 nucleosome. At thousands of genes, RNA polymerase II engages the +1 nucleosome and pauses. How the transcription initiation machinery contends with the +1 nucleosome appears to be fundamentally different between lower and higher eukaryotes.Knowledge of the precise location of nucleosomes in a genome is essential in order to understand the context in which chromosomal processes such as transcription and DNA replication operate. A common theme to emerge from recent genome-wide maps of nucleosome locations is a general deficiency of nucleosomes in promoter regions and an enrichment of certain histone modifications towards the 5′ end of genes [1][2][3][4][5][6][7] . A high resolution genomic map of nucleosome locations in the budding yeast S. cerevisiae has further revealed Correspondence and request for material should be addressed to B.F.P. (bfp2@psu.edu). * These authors contributed equally to this work.Author Information Sequence data deposition is through NCBI Trace Archives TI SRA000283, Sequencing Center = "CCGB", and microarray deposition through ArrayExpress, Accession numbers E-MEXP-1515 and -1519. Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interest.Author Contributions T.M. prepared and purified the nucleosomes including Pol II-bound nucleosomes; C.J. analyzed the nucleosome mapping data and its relationship to other genomic features; I.P.I. performed computational analyses related to nucleosome positioning sequences; X.L. conducted ChIP-chip on Pol II; B.J.V. conducted ChIP-chip on nucleosome-Pol II interactions; S.J.Z. provided bioinformatics support; L.T. constructed libraries and sequenced nucleosomal DNA; J.Q. mapped sequencing reads to the yeast genome; RG provided H2A.Z antibodies; SCS directed the DNA sequencing phase; DSG directed embryo preparations and helped interpret the data; I.A. developed computational approaches to derive nucleosome maps from the read locations and developed the associated browser; B.F.P. directed the project, interpreted the data, and wrote the paper. S6). Those 112,750 nucleosomes detected three or more times were further analyzed, although patterns were identical when all nucleosomes were analyzed. The internal median error of the data was 4 bp (Fig. S7). H2A.Z nucleosomes were predominantly distributed at 175 bp intervals from the TSS (compared to 165 ...

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“…H2A.Z levels correlated with gene expression (Figs. 1c and S9), as has been seen on individual genes and in Saccharomyces 12,13,17 .…”

supporting

confidence: 58%

Nucleosome organization in the Drosophila genome

Mavrich

Jiang

Ioshikhes

et al. 2008

Nature

662

690

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“…H2A.Z is also preferentially incorporated at promoters in yeast and at promoters of some developmentally regulated and actively expressed genes (Bruce et al 2005) in chicken. It seemed important, therefore, to determine the frequency with which H3.3 and H2A.Z were found at the same site.…”

Section: Genomic Location Of H33/h2az Ncpsmentioning

confidence: 99%

“…H2Av, the H2A.Z of Drosophila, is involved in Polycomb-mediated silencing and establishment of centromeric heterochromatin (Swaminathan et al 2005). In chicken erythroid cells, H2A.Z appears to be concentrated at promoters of developmentally regulated and actively expressed genes (Bruce et al 2005), while at the human c-myc locus, H2A.Z is always enriched at the promoter, whether or not c-myc expression is induced, but is lost from the coding region after induction (Farris et al 2005).…”

mentioning

confidence: 99%

Nucleosome stability mediated by histone variants H3.3 and H2A.Z

Jin

Felsenfeld²

2007

Genes Dev.

502

462

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Nucleosomes containing the histone variant H3.3 tend to be clustered in vivo in the neighborhood of transcriptionally active genes and over regulatory elements. It has not been clear, however, whether H3.3-containing nucleosomes possess unique properties that would affect transcription. We report here that H3.3 nucleosomes isolated from vertebrates, regardless of whether they are partnered with H2A or H2A.Z, are unusually sensitive to salt-dependent disruption, losing H2A/H2B or H2A.Z/H2B dimers. Immunoprecipitation studies of nucleosome core particles (NCPs) show that NCPs that contain both H3.3 and H2A.Z are even less stable than NCPs containing H3.3 and H2A. Intriguingly, NCPs containing H3 and H2A.Z are at least as stable as H3/H2A NCPs. These results establish an hierarchy of stabilities for native nucleosomes carrying different complements of variants, and suggest how H2A.Z could play different roles depending on its partners within the NCP. They also are consistent with the idea that H3.3 plays an active role in maintaining accessible chromatin structures in enhancer regions and transcribed regions. Consistent with this idea, promoters and enhancers at transcriptionally active genes and coding regions at highly expressed genes have nucleosomes that simultaneously carry both H3.3 and H2A.Z, and should therefore be extremely sensitive to disruption.

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“…H2A.Z levels have been found to correlate with both active and repressed states of gene expression. For example, H2A.Z is enriched at active gene promoters, as well as at enhancer and insulator elements in terminally differentiated cells from chicken, mouse, and human, suggesting a positive role in regulating gene expression (Bruce et al 2005;Thambirajah et al 2006;Barski et al 2007). Indeed, activation of a gene often includes promoter chromatin remodeling and incorporation of H2A.Z into nucleosomes surrounding the transcriptional start site (TSS) (Gevry et al 2009;Hardy et al 2009).…”

mentioning

confidence: 99%

Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis

Conerly¹,

Teves²,

Diolaiti³

et al. 2010

Genome Res.

118

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The histone variant H2A.Z has been implicated in the regulation of gene expression, and in plants antagonizes DNA methylation. Here, we ask whether a similar relationship exists in mammals, using a mouse B-cell lymphoma model, where chromatin states can be monitored during tumorigenesis. Using native chromatin immunoprecipitation with microarray hybridization (ChIP-chip), we found a progressive depletion of H2A.Z around transcriptional start sites (TSSs) during MYC-induced transformation of pre-B cells and, subsequently, during lymphomagenesis. In addition, we found that H2A.Z and DNA methylation are generally anticorrelated around TSSs in both wild-type and MYC-transformed cells, as expected for the opposite effects of these chromatin features on promoter competence. Depletion of H2A.Z over TSSs both in cells that are induced to proliferate and in cells that are developing into a tumor suggests that progressive loss of H2A.Z during tumorigenesis results from the advancing disease state. These changes were accompanied by increases in chromatin salt solubility. Surprisingly,~30% of all genes showed a redistribution of H2A.Z from around TSSs to bodies of active genes during the transition from MYC-transformed to tumor cells, with DNA methylation lost from gene bodies where H2A.Z levels increased. No such redistributions were observed during MYC-induced transformation of wild-type pre-B cells. The documented role of H2A.Z in regulating transcription suggests that 30% of genes have the potential to be aberrantly expressed during tumorigenesis. Our results imply that antagonism between H2A.Z deposition and DNA methylation is a conserved feature of eukaryotic genes, and that transcription-coupled H2A.Z changes may play a role in cancer initiation and progression.

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The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken

Cited by 146 publications

References 31 publications

Nucleosome organization in the Drosophila genome

Nucleosome organization in the Drosophila genome

Nucleosome stability mediated by histone variants H3.3 and H2A.Z

Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis

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